Various radioactive cyclic nucleotide derivatives will be synthesized and their metabolism will be examined in hepatoma cells. The ara- and 2'deoxy- versions of the 8-amino substituted cyclic nucleotides will be synthesized and tested for cytotoxicity. Variant cells resistant to all of the cytotoxic cyclic nucleotide derivatives will be cloned for analysis of possible differences in the metabolism of these derivatives as well as for cross-resistance and complementation studies. Preliminary experiments will be performed on: a) The cell cycle specificity of the cytotoxic cyclic nucleotides. b) The effects of the cytotoxic cyclic nucleotides on purine-pyrimidine interconversions and de novo synthesis. c) The toxicity and efficacy of the cyclic nucleotide derivatives in tumor-bearing animals.